Survivals of transplants between unrelated humans do not appear to correlate well with tissue antigen matching as defined by present testing methods. One proposed explanation for this discrepancy is the host immune reaction against donor tissue antigens not identified by the present lymphocyte dependent assays. We intend to explore this possibility employing a technique in which donor tissue slices are grafted to host kidneys. These grafts will span several genetic barriers in lines of the house mouse (Mus musculus). Our objective will be to define the genetically determined antigenic system(s) critical in rejection of specific tissues in the mouse. This information hopefully will serve to direct us toward a similar system in man. Grafts will be histologically evaluated by photometric methods in order to score rejection by lymphocyte infiltration. The origin of cells (host or donor) which appear to be repopulating the graft will be determined using chromosomal markers and the qualitative and quantitative relationship between repopulating cells and the time course of the rejection process will be studied. Both rejection and host cell repopulation of the graft will be utilized to identify the genetic barrier(s) most important to the immune response of the host against a particular grafted tissue.